FDA Draft Guidance on Container Closure Systems: Key Considerations for Drug Developers

FDA’s New Draft Guidance on Container Closure Systems: What Drug Developers Need to Know

A risk-based approach puts packaging suitability, compatibility and performance firmly within the broader CMC strategy

For nearly three decades, the FDA’s approach to container closure systems (CCSs) for human drugs and biological products has been guided by recommendations first issued in 1999. In August 2026, the U.S. Food and Drug Administration (FDA) issued a new draft guidance, “Container Closure Systems for Human Drugs and Biological Products,” proposing a modernized, risk-based framework for evaluating the quality of packaging systems used for drugs and biologics.

The draft, developed by FDA’s Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), and Office of Combination Products (OCP), is intended to supersede the 1999 guidance and its 2002 Questions and Answers when finalized. The draft is currently nonbinding and not for implementation, with FDA accepting comments through October 13, 2026.

For sponsors developing complex formulations, biologics, combination products and products with sensitive delivery requirements, the implications extend beyond packaging selection. The guidance reinforces an important principle: the container closure system is part of the product’s quality strategy.

This analysis incorporates key insights from Mallikaarjunan, Senior Vice President of Regulatory Affairs & Technology, Navitas Life Sciences, on the practical implications of the FDA’s proposed risk-based approach to container closure systems.

Why the guidance matters

A container closure system can influence the drug product’s stability, quality, safety, integrity and, in some cases, delivery performance.

FDA’s draft guidance therefore frames CCS evaluation around a product-specific risk assessment rather than a universal testing checklist. The assessment should consider factors including the materials of construction, potential interactions between the packaging and drug product, manufacturing processes, storage and handling conditions, and the intended route of administration.

This represents a meaningful shift in emphasis: rather than asking only whether a packaging component meets a predefined specification, sponsors need to consider whether the complete CCS is suitable for its intended product and use.

1. From packaging selection to risk-based CCS assessment

The draft guidance organizes CCS assessment around several dimensions:

• Safety of packaging materials
• Protection of the drug product
• CCS performance and functionality
• Impact of manufacturing processes
• Storage and handling conditions

The risk assessment is expected to be tailored to the product. For example, a packaging system for an oral solid dosage form may present a different risk profile from one used for a sterile injectable, inhalation product or biologic requiring frozen storage.

This product-specific approach is particularly relevant as drug development increasingly encompasses complex molecules, sensitive biologics, novel delivery systems and combination products.

2. Packaging materials become a quality consideration

The choice of materials of construction (MOC) is central to CCS suitability.

The draft calls for identification of materials such as glass, plastics, metals, elastomers, coatings and adhesives, together with relevant manufacturer and material information. It also specifically states that postconsumer recycled plastic should not be used in primary packaging components; where such material is used in secondary packaging, its suitability must be addressed.

For sponsors, this reinforces the need to understand not only the identity of packaging materials, but also their potential interaction with the drug product and the effects of processing, storage and use.

3. Extractables and leachables move closer to the center of CCS strategy

One of the most important areas highlighted in the draft is extractables and leachables (E&L).

FDA describes E&L assessment as an integral part of CCS suitability evaluation for products likely to interact with packaging components. The draft recommends a risk-based, product-specific approach to designing E&L studies and associated toxicological assessments.

Importantly, the draft recognizes that leachables assessment can extend across the product’s shelf life. Studies may involve multiple batches and time points under long-term and accelerated stability conditions, with the CCS used in testing representative of the future commercial product.

This has implications for development planning. E&L cannot always be treated as an isolated analytical exercise conducted immediately before submission. For products with meaningful packaging interaction risk, packaging selection, formulation development, analytical characterization, toxicological assessment and stability strategy may need to be considered together.

4. The CCS must protect

FDA expects CCSs to protect drug products against factors such as:

• Light exposure
• Oxygen and other reactive gases
• Moisture
• Microbial ingress
• Solvent loss
• Physical stresses during transportation and storage
• Leakage and loss of container closure integrity

The CCS must also perform its intended function. For example, closures used repeatedly may require evaluation of characteristics such as penetrability, fragmentation and self-sealing performance. For delivery systems, performance may also include the ability to deliver the drug at the intended site, amount and rate.

This distinction between protection and performance becomes especially important for products where packaging is closely linked to drug delivery.

5. Dosage form and route of administration matter

The FDA draft recognizes that CCS risks vary significantly across dosage forms.

It provides specific considerations for:

• Inhalation products
• Intranasal products
• Injectable products
• Transdermal and transmucosal delivery systems
• Topical products
• Ophthalmic and otic products
• Oral products

For inhalation products in particular, the CCS and delivery system can have a direct influence on product performance and patient exposure. FDA notes that metered-dose inhaler CCSs can contribute to aerosol generation, aerosol characteristics and the amount of medication delivered.

This makes the packaging-development interface particularly important for inhaled therapies, combination products and other drug-device systems, where packaging and delivery performance can be closely interconnected.

6. Manufacturing and storage conditions cannot be considered separately

A CCS that is suitable before manufacturing may behave differently after exposure to manufacturing processes.

The draft recommends evaluating the potential effects of processes such as washing, coating, sterilization, lyophilization and depyrogenation on CCS suitability, compatibility and functionality. High heat, irradiation or reactive gases, for example, may affect packaging materials or contribute to chemical migration.

Storage and handling conditions are equally important. For products stored at very low or cryogenic temperatures, FDA recommends assessing CCS integrity and functionality under worst-case conditions, including through approaches such as freeze-thaw or thermal cycling where appropriate.

For sponsors developing biologics and other temperature-sensitive products, this reinforces the importance of considering the entire product lifecycle, from manufacturing through distribution and storage.

7. Shipping validation is part of the picture

A CCS must maintain its integrity not only on the manufacturing line but throughout transportation and storage.

The draft identifies additional testing that may be appropriate for assembled CCSs, including shipping validation or qualification, freeze-thaw testing and thermal cycling.

This is particularly relevant for products exposed to complex global supply chains, temperature excursions or significant mechanical stresses during distribution.

Packaging therefore becomes part of the broader product lifecycle and supply-chain risk strategy, rather than simply an element of final presentation.

From compliance exercise to development strategy

The FDA’s draft guidance signals a broader change in pharmaceutical quality: packaging suitability should be demonstrated through science, risk assessment and product-specific evidence.

For innovative drug products, the CCS may interact with formulation, manufacturing, stability, delivery performance and patient safety in ways that cannot be adequately assessed in isolation.

That makes early integration between CMC, analytical, toxicology, regulatory and packaging expertise increasingly important.

How Navitas Life Sciences Can Help

The FDA’s proposed risk-based approach to container closure systems reinforces the importance of building packaging-related evidence and justification into the broader CMC and regulatory strategy early in development. For sponsors, this means ensuring that information on materials of construction, product-package interactions, extractables and leachables, container closure integrity, stability and transportation considerations is appropriately assessed, documented and positioned within the regulatory dossier.

Navitas Life Sciences supports sponsors through the regulatory submission lifecycle, helping translate complex development information into structured, submission-ready documentation. With 250+ regulatory professionals, Navitas provides expertise across document authoring, CTD compilation, eCTD publishing, submission management and post-approval regulatory activities for drugs, biologics and other healthcare products.

Through its regulatory submission management and publishing capabilities, Navitas can help sponsors:

• Structure and compile CMC information relevant to packaging and container closure systems within the appropriate CTD sections.
• Integrate supporting documentation and technical evidence into regulatory submissions while maintaining consistency, traceability and document quality.
• Manage submission publishing and lifecycle activities using validated regulatory technology, including pharmaREADY®.
• Support global regulatory submissions and post-approval changes, helping sponsors maintain regulatory alignment as product and packaging strategies evolve.
• Bring regulatory expertise into development planning early, helping identify documentation and evidence considerations before they become submission-stage challenges.

With experience supporting IND, NDA, ANDA, BLA, MAA, CTA and DMF submissions, Navitas combines regulatory expertise, technology-enabled publishing and lifecycle support to help sponsors manage increasingly complex regulatory expectations.

For sponsors developing innovative drugs and biologics, early regulatory alignment can turn complex CMC requirements into a more predictable path to submission and approval.

 

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